The possible role of zinc and metallothionein in the liver on the therapeutic effect of IFN-α to hepatitis C patients

We have studied zinc deficiency in hepatitis C patients (complete responder [C,R] 22, nonresponder [NR] 25) with relation to the therapeutic effect of interferon-α (IFN-α). Circadian variations in serum zinc levels were high in the morning (basal level) and then gradually decreased during the day in both chronic hepatitis C patients and healthy controls. Basal zinc levels in serum were significantly lower in chronic hepatitis C patients (73±3 μg/dL,n=12) than in controls (93±5 μg/dL). An injection of 10 MU of IFN-α to hepatitis C patients augmented the serum zinc reductions, up to 40% in 8 h. Serum cortisol levels were significantly elevated 8 h (25.6±2.3 μg/dL) after IFN-α dose. Forty-seven chronic hepatitis C patients were treated with IFN-α for 24 wk, and serum zinc and copper levels were determined 12 and 24 wk during and after the completion of IFN-α therapy. Serum zinc levels and zinc/copper ratio were higher in CRs than in NRs to IFN therapy at each time-point. Hepatic metallothionein staining became prominent after IFN therapy in most of CRs, whereas it diminished NRs. These data suggest that nutritional status of zinc influences the effect of IFN on hepatitis C patients.     

Highly potent cell differentiation-inducing analogues of 1alpha,25-dihydroxyvitamin D3: synthesis and biological activity of 2-methyl-1,25-dihydroxyvitamin D3 with side-chain modifications

Eight 2-methyl substituted analogues of 20-epi-22R-methyl-1alpha,25-dihydroxyvitamin D3 (5) and 20-epi-24,26,27-trihomo-22-oxa-1alpha,25-dihydroxyvitamin D3 (6: KH-1060) were convergently synthesized. Preparation of the CD-ring portions with modified side chains of 5 and 6, followed by palladium-catalyzed cross-coupling with the A-ring enyne synthons (20a-d), (3S,4S,5R)-, (3S,4R,5R)-, (3S,4S,5S)- and (3R,4R,5S)-3,5-bis[(tert-butyldimethylsilyl)oxy]-4-methyloct-1-en-7-yne, afforded two sets of four A-ring stereoisomers of 20-epi-2,22-dimethyl-1,25-dihydroxyvitamin D3 (7a-d) and 20-epi-24,26,27-trihomo-2-methyl-22-oxa-1,25-dihydroxyvitamin D3 (8a-d). The biological profiles of the hybrid analogues were assessed in terms of affinity for vitamin D receptor (VDR) and HL-60 cell differentiation-inducing activity in comparison with the natural hormone. The combined modifications of the A-ring at the 2-position and the side chain yielded analogues with high potency.     

New onset and natural remission of excessive daytime sleepiness and its correlates among high-school students

Sleep and Biological Rhythms - Excessive daytime sleepiness (EDS) is highly prevalent among high-school students, and preventa-tive measures against it are essential for promotion of school health....     

Live Imaging-Based Model Selection Reveals Periodic Regulation of the Stochastic G1/S Phase Transition in Vertebrate Axial Development

In multicellular organism development, a stochastic cellular response is observed, even when a population of cells is exposed to the same environmental conditions. Retrieving the spatiotemporal regulatory mode hidden in the heterogeneous cellular behavior is a challenging task. The G1/S transition observed in cell cycle progression is a highly stochastic process. By taking advantage of a fluorescence cell cycle indicator, Fucci technology, we aimed to unveil a hidden regulatory mode of cell cycle progression in developing zebrafish. Fluorescence live imaging of Cecyil, a zebrafish line genetically expressing Fucci, demonstrated that newly formed notochordal cells from the posterior tip of the embryonic mesoderm exhibited the red (G1) fluorescence signal in the developing notochord. Prior to their initial vacuolation, these cells showed a fluorescence color switch from red to green, indicating G1/S transitions. This G1/S transition did not occur in a synchronous manner, but rather exhibited a stochastic process, since a mixed population of red and green cells was always inserted between newly formed red (G1) notochordal cells and vacuolating green cells. We termed this mixed population of notochordal cells, the G1/S transition window. We first performed quantitative analyses of live imaging data and a numerical estimation of the probability of the G1/S transition, which demonstrated the existence of a posteriorly traveling regulatory wave of the G1/S transition window. To obtain a better understanding of this regulatory mode, we constructed a mathematical model and performed a model selection by comparing the results obtained from the models with those from the experimental data. Our analyses demonstrated that the stochastic G1/S transition window in the notochord travels posteriorly in a periodic fashion, with doubled the periodicity of the neighboring paraxial mesoderm segmentation. This approach may have implications for the characterization of the pathophysiological tissue growth mode.     

Factors determining prognosis in streptococcal toxic shock-like syndrome: results of a nationwide investigation in Japan

Since the first report of streptococcal toxic shock-like syndrome (TSLS) in Japan, the numbers of reported patients have been increasing. However, clinical manifestations remain somewhat unclear, and factors potentially defining prognosis remain to be identified. We conducted a retrospective nationwide postal survey of major Japanese hospitals concerning clinical manifestations of invasive streptococcal infections including necrotizing fasciitis and TSLS. We evaluated 30 patients who died and 36 survivors. The overall mortality rate was 45%. Physical and laboratory findings on admission were compared statistically between fatal cases and surviving patients. Most laboratory results from the patients who died showed greater abnormality than results from the survivors. Patients who died had significantly fewer leukocytes and platelets, although their C-reactive protein concentrations were similar to those in survivors. Creatinine was significantly higher, and temperature and blood pressure were significantly lower, in patients who died. Patients with invasive streptococcal infections should be managed aggressively when the above features are present.     

Stemar-13-ene synthase, a diterpene cyclase involved in the biosynthesis of the phytoalexin oryzalexin S in rice

In suspension-cultured rice cells, diterpenoid phytoalexins are produced in response to exogenously applied elicitors. We isolated a cDNA encoding a diterpene cyclase, OsDTC2, from suspension-cultured rice cells treated with a chitin elicitor. The OsDTC2 cDNA was overexpressed in Escherichia coli as a fusion protein with glutathione S-transferase, and the recombinant OsDTC2 was indicated to function as stemar-13-ene synthase that converted syn-copalyl diphosphate to stemar-13-ene, a putative diterpene hydrocarbon precursor of the phytoalexin oryzalexin S. The level of OsDTC2 mRNA in suspension-cultured rice cells began to increase 3 h after addition of the elicitor and reached the maximum after 8 h. The expression of OsDTC2 was also induced in UV-irradiated rice leaves. In addition, we indicated that stemar-13-ene accumulated in the chitin-elicited suspension-cultured rice cells and the UV-irradiated rice leaves.     

Molecular mechanism of self-recognition in Brassica self-incompatibility

In most self-incompatible plant species, recognition of self-pollen is controlled by a single locus, termed the S-locus. In Brassica, genetic dissection of the S-locus has revealed the presence of three highly-polymorphic genes: S-receptor kinase (SRK), S-locus protein 11 (SP11) (also known as S-locus cysteine-rich protein; SCR) and S-locus glycoprotein (SLG). SRK encodes a membrane-spanning serine/threonine kinase that determines the S-haplotype specificity of the stigma. SP11 encodes a small cysteine-rich protein that determines the S-haplotype specificity of pollen. SLG encodes a secreted form of stigma protein similar to the extracellular domain of SRK. Recent biochemical studies have revealed that SP11 functions as the sole ligand for its cognate SRK receptor complex. Their interaction induces the autophosphorylation of SRK, which is expected to trigger the signalling cascade that results in the rejection of self-pollen. This so-called ligand-receptor complex interaction and receptor activation occur in an S-haplotype-specific manner, and this specificity is almost certainly the basis for self-pollen recognition.